Epigenetics of Perinatal Asphyxia and Therapeutic Hypothermia

Hypoxic-ischemic insults in the perinatal period rank globally as the second leading cause of newborn mortality. A large proportion of newborns that survive the initial insult develop brain dysfunctions known as hypoxic-ischemic encephalopathy (HIE). At present, therapeutic
hypothermia is the only treatment available to minimize the consequences of HIE. Despite cooling, the risk of death or severe neurodisability is still high and additional neuroprotective strategies are greatly needed. Further, determining the exact aetiology and the timing of brain injury is often challenging and might preclude optimal treatment. Research aimed at i) identifying novel biomarkers that could provide reliable information about the timing and nature of brain injury and ii) gaining insight into the pathophysiology of HIE could improve patient outcome. In view of this notion, this thesis investigated the role of epigenetic (dys)regulation in hypoxic-ischemic brain damage and hypothermia-induced neuroprotection making use of well-established animal models of perinatal hypoxia-ischemia.